Platelet activating factor. Stimulation of the lipoxygenase pathway in polymorphonuclear leukocytes by 1-O-alkyl-2-O-acetyl-sn-glycero-3-phosphocholine.
1-O-Alkyl-2-O-acetyl-sn-glycero-3-phosphocholine (AAGPC) triggered the release of [3H]arachidonate but not [14C]stearate from cellular phospholipids in cytochalasin B-treated rabbit polymorphonuclear leukocytes. Concentrations of AAGPC up to 20 nM caused a dose-dependent release and subsequent metabolism of the released [3H]arachidonic acid. Most of the release of the [3H]arachidonate had taken place within the first 2 min of stimulation. Phosphatidylinositol and phosphatidylcholine served as the sources of [3H]arachidonate with about 50% of the label coming from each pool. Challenge of cytochalasin B-treated polymorphonuclear leukocytes with AAPGC led to the production of [3H]hydroxyeicosatetraenoic acids and [3H]dihydroxyeicosatetraenoic acids. No significant production of [3H]prostaglandins or [3H]thromboxanes was detected. AAGPC also caused a dose-dependent degranulation of cytochalasin B-treated rabbit polymorphonuclear leukocytes as shown by the release of beta-glucuronidase and lysozyme. Both the AAGPC-stimulated production of arachidonate metabolites and the degranulation response were blocked by eicosatetraynoic acid and non-dihydroguaiaretic acid at similar inhibitor concentrations. These findings suggest the bioactions of AAGPC on polymorphonuclear leukocytes may be mediated by the release of arachidonic acid and the production of mono- and dihydroxyeicosatetraenoic acids.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001779:Blood Coagulation Factors / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002417:Cattle; D003571:Cytochalasin B / Q000494:pharmacology; D005966:Glucuronidase / Q000378:metabolism; D007700:Kinetics; D008084:Lipoxygenase / Q000378:metabolism*; D008244:Lysophosphatidylcholines / Q000302:isolation & purification / Q000494:pharmacology*; D009113:Muramidase / Q000378:metabolism; D009206:Myocardium; D009504:Neutrophils / Q000187:drug effects / Q000201:enzymology*; D010972:Platelet Activating Factor; D011817:Rabbits
D001095:Arachidonic Acids; D001779:Blood Coagulation Factors; D008244:Lysophosphatidylcholines; D010972:Platelet Activating Factor; D016718:Arachidonic Acid; D000001:Calcimycin; D003571:Cytochalasin B; D008084:Lipoxygenase; D009113:Muramidase; D005966:Glucuronidase